Pediatric Heart Transplant Candidates Research Articles

Taking a Closer Look at Distance: Does Increasing the Maximal Donor Distance Range Shorten Waitlist Times in Pediatric Heart Transplant Candidates?

<h3>Purpose</h3> Data suggest that pediatric heart transplant (HT) centers can reduce waitlist time by expanding donor catchment vis expanded parameters including the maximal donor weight range. Contrary to donor weight ranges, little is known about the effect of increasing the donor distance (DD) range. We sought to determine whether increasing the DD range can reduce waitlist time and how well actual DD predicts ischemic time (IT). <h3>Methods</h3> All US children <18 years listed for HT at centers with ≥20 HT since 2007 were identified using OPTN data. Center variation in maximal DD range, defined as the median value of a center's maximal DD range, was analyzed and compared to actual DD. Pearson correlation was used to examine the correlation between actual DD and IT. Cox proportional hazards analysis was used to determine whether maximal DD range is associated with waitlist time. <h3>Results</h3> Among 4,240 children who met study criteria, the median age was 2 (IQR 0, 11) years, weight 12 (6, 35) kg, 53% had CHD. Centers varied considerably in their maximal DD range (1000-10,000 miles); median 1500 miles (Figure A). Overall, 86% of donors originated from ≤500 miles; 97% ≤1,000 miles (Figures A & B) with sharp drop-offs at 500 and 1000 miles (Figure B). After adjusting for patient factors, maximal DD range was associated with a shorter waitlist time. The correlation between actual DD and IT is fair (R=0.69) but explains only half (R²=0.49) of the variability in IT. <h3>Conclusion</h3> Pediatric HT centers vary considerably in their maximal donor distance ranges, though most donors still fall within 500-1000 miles of recipients. Increasing the maximal DD range appears is associated with a shorter waitlist time. Actual DD explains only half of the variability in IT. Further research is needed to understand the optimal regional sharing distance for organ allocation and whether contemporary navigational software could better predict IT than the linear distance to the donor hospital.

Pediatric Risk to OHT (PRO) Score: Insights from UNOS Waitlist Mortality Findings

<h3>Purpose</h3> Waitlisted pediatric heart transplant candidates have the highest mortality rate amongst solid organ transplants. The current criteria in the United States provides equal weight to a patient's medical severity and waitlist time. A risk score much like the Model for End Stage Liver Disease (MELD) score utilized for patients awaiting liver transplant would incorporate a candidate's unique risk factors to predict mortality on the waitlist and optimize organ allocation to the sickest awaiting transplantation. <h3>Methods</h3> Utilizing the United Network for Organ Sharing (UNOS) database, a total of 5557 patients aged 0-18 years old on the waitlist for a single, first time, heart transplant from January 2010-June 2019 were evaluated. A univariate analysis was performed on two-thirds (N=3705) of these patients to derive the factors most associated with waitlist mortality or delisting within 1 year. Those with a p-value < 0.2 underwent a multivariate analysis and the resulting factors were used to build a prediction model using the Fine-Grey model analysis. This predictive scoring model was validated on the remaining one-third of the patients (N=1852). <h3>Results</h3> The Pediatric Risk to OHT (PRO) scoring model utilized the following unique patient variables: blood type, diagnosis of congenital heart disease, weight, ventilator support, inotropic support, extracorporeal membrane oxygenation (ECMO) status, creatinine level, and region (Figure 1A). A higher score indicates an increased risk of mortality. The PRO score had a predictive strength of 0.745 as measured by Area Under the ROC curve at 1 year (Figure 1B). The derivation group had a PRO score mean of 1.35 (standard deviation 0.88) and median of 1.39; the validation group had a comparable PRO score mean of 1.33 (standard deviation of 0.90) and median of 1.35. <h3>Conclusion</h3> The PRO score is an improved predictive model to better assess the mortality for patients awaiting heart transplant. With prospective application, this study aims to improve allocation of a limited resource.

The Waiting List Mortality of Pediatric Heart Transplantation Candidates in Korea before the Pediatric Ventricular Assist Device Era.

BackgroundDespite advancements in heart transplantation for pediatric patients in Korea, the waiting list mortality has not been reported. Therefore, we investigated the waiting list mortality rate and factors associated with patient mortality.MethodsWe reviewed the medical records of pediatric patients who were registered for heart transplantation at three major hospitals in Korea from January 2000 to January 2020. All patients who died while waiting for heart transplantation were investigated, and we identified the waiting list mortality rate, causes of mortality and median survival periods depending on the variable risk factors.ResultsA total of 145 patients received heart transplantations at the three institutions we surveyed, and the waiting list mortality rate was 26%. The most common underlying diseases were cardiomyopathy (66.7%) and congenital heart disease (30.3%). The leading causes that contributed to death were heart failure (36.3%), multi-organ failure (27.2%), and complications associated with extracorporeal membrane oxygenation (ECMO) (25.7%). The median survival period was 63 days. ECMO was applied in 30 patients. The different waiting list mortality percentages according to age, cardiac diagnosis, use of ECMO, and initial Korean Network of Organ Sharing (KONOS) level were determined using univariate analysis, but age was the only significant factor associated with waiting list mortality based on a multivariate analysis.ConclusionThe waiting list mortality of pediatric heart transplantation candidates was confirmed to be considerably high, and age, underlying disease, the application of ECMO, and the initial KONOS level were the factors that influenced the survival period.

Impact of mechanical circulatory support on pediatric heart transplant candidates with elevated pulmonary vascular resistance.

With the new era of increasing use of mechanical circulatory support (MCS) in children, seemingly more patients with elevated pulmonary vascular resistance (PVR) are having positive outcomes. The purpose of this study was to define the effect of MCS on pediatric patients listed for heart transplant with an elevated PVR. The United Network for Organ Sharing (UNOS) database was used to identify patients aged 0-18 at the time of listing for heart transplant between 2010 and 2019 who had PVR documented (n = 2081). Patients were divided into MCS (LVAD, RVAD, BiVAD, and TAH) and No MCS groups, then divided by PVR (PVR) at the time of listing: <3, 3-6, and >6 Wood units (WU). MCS was used in 20% overall (n = 426); 57% of those with PVR <3, 27% with PVR 3-6, and 16% with PVR >6. MCS, PVR <3 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .049; vs. PVR 3-6, P = .004; vs. PVR >6, P < .001). MCS, PVR 3-6 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR <3, P = .048; vs. PVR 3-6, P = .009; vs. PVR >6, P < .001). MCS, PVR >6 patients had a higher chance of positive waitlist outcome than No MCS, PVR >6 patients (P = .012). Within the No MCS group, patients with a PVR >6 had a higher incidence of negative waitlist outcome compared to PVR <3 (17% vs. 10%, P = .002); this was not the case in the MCS group (5% vs. 6%, P = .693). More patients in the MCS group were ventilator dependent (15% vs. 9%, P < .001) at the time of listing and less likely to have a functional status >50% (43% vs. 73%, P < .001). No significant differences in post-transplant survival were found in pairwise comparisons of MCS and No MCS PVR subgroups. Patients supported with MCS had a significantly higher chance of a positive waitlist outcome than those without such support regardless of PVR status. This was most pronounced with a PVR greater than 6 WU. MCS compared to No MCS patients had better waitlist survival and equivalent post-transplant survival. MCS patients, despite being more ill, had better overall survival regardless of PVR.

Taking a Closer Look at Distance: Does Increasing the Maximal Donor Distance Range Shorten Waitlist Times in Pediatric Heart Transplant Candidates?

Data suggest that pediatric heart transplant (HT) centers can reduce waitlist time by expanding donor catchment via expanded parameters including the maximal donor weight range. Contrary to donor weight ranges, little is known about the effect of increasing the donor distance (DD) range. We sought to determine whether increasing the DD range can reduce waitlist time and how well actual DD predicts ischemic time (IT). All US children <18 years listed for HT at centers with ≥20 HT since 2007 were identified using OPTN data. Center variation in maximal DD range, defined as the median value of a center's maximal DD range, was analyzed and compared to actual DD. Pearson correlation was used to examine the correlation between actual DD and IT. Cox proportional hazards analysis was used to determine whether maximal DD range is associated with waitlist time. Among 4,240 children who met study criteria, the median age was 2 (IQR 0, 11) years, weight 12 (6, 35) kg, 53% had CHD. Centers varied considerably in their maximal DD range (1000-10,000 miles); median 1500 miles (Figure A). Overall, 86% of donors originated from ≤500 miles; 97% ≤1,000 miles (Figures A & B) with sharp drop-offs at 500 and 1000 miles (Figure B). After adjusting for patient factors, maximal DD range was associated with a shorter waitlist time. The correlation between actual DD and IT is fair (R=0.69) but explains only half (R2=0.49) of the variability in IT. Pediatric HT centers vary considerably in their maximal donor distance ranges, though most donors still fall within 500-1000 miles of recipients. Increasing the maximal DD range is associated with a shorter waitlist time. Actual DD explains only half of the variability in IT. Further research is needed to understand the optimal regional sharing distance for organ allocation and whether contemporary navigational software could better predict IT than the linear distance to the donor hospital.

Impact of Mechanical Circulatory Support on Pediatric Heart Transplant Candidates with Elevated Pulmonary Vascular Resistance

With the new era of more effective medicines and increasing use of mechanical circulatory support (MCS) in children, seemingly more patients with elevated pulmonary vascular resistance (PVR) are having positive outcomes. The purpose of this study is to define the effect of MCS on pediatric patients listed for heart transplant with an elevated PVR. The United Network for Organ Sharing (UNOS) database was used to identify patients ages 0-18 at time of listing for heart transplant between 2010 and 2019 who had PVR documented. Patients were divided into MCS (LVAD, RVAD, BiVAD, and TAH) and No-MCS groups, then divided by indexed PVR (PVRi) at time of listing: <3, 3-6, and >6 Wood units. Positive waitlist outcome was defined as reaching transplant or delisted because of clinical improvement. Negative waitlist outcome was defined as death or delisted because too sick to transplant. 2081 pediatric patients were listed for heart transplant between 2010 and 2019. MCS was used in 20% overall (n=426); 57% of those with PVRi <3, 27% with PVRi 3-6, and 16% with PVRi >6. Median MCS duration was 68 days (IQR 30-142). In all three PVRi groups, MCS patients had a significantly higher incidence of positive waitlist outcome compared to No-MCS patients (Table 1). Within the No-MCS group, patients with a PVRi >6 had a higher incidence of negative waitlist outcome compared to PVRi <3 (17 vs 10%, p=0.002). This was not true in the MCS group (5 vs 6%, p=0.693). No significant differences in post-transplant survival were found between the subgroups. Patients supported with MCS had a significantly higher chance of a positive waitlist outcome than those without such support regardless of PVR status. With better waitlist survival and equivalent post-transplant survival compared to No-MCS patients, MCS patients had better overall survival from listing regardless of PVR.

Insurance Type and Impact on Waitlist Mortality in Young Heart Transplant Candidates: A UNOS Registry Analysis

Public insurance increasingly funds adult heart transplants but does not impact their waitlist mortality. Insurance trends and their impact on waitlist mortality are not yet described in children. Using the OPTN/UNOS database, we described characteristics of pediatric (<18 years) and young adult (18-26 years) heart transplant candidates in three 5-year eras ('03-'08; '08-'13; '13-'18). Waitlist mortality was analyzed by competing outcomes analysis. Risk factors for mortality were identified using competing risks regression. We identified 10,466 pediatric (79%) and young adult (21%) candidates. The proportion of pediatric patients covered by public insurance (mostly Medicaid) increased (Figure 1, p<0.001). This trend persisted in all pediatric age groups and diagnoses. In contrast, young adults used more private insurance from Era 1 to Era 2 (p=0.001). Though public insurance increased in both white and black candidates, insurance was predominantly private in white candidates and public in black candidates. Waitlist mortality decreased across eras (subdistribution hazard ratio [SHR] 0.86, p<0.001); however public health insurance at listing was associated with increased waitlist mortality after adjusting for era (SHR 1.19, p=0.001, Figure 2). Pediatric heart transplant candidates are increasingly covered by public health insurance. Despite lower waitlist mortality overall, public health insurance at listing is associated with inferior waitlist survival. These results differ significantly from data in adult candidates and warrant further investigation.

Marijuana in pediatric and adult congenital heart disease heart transplant listing: A survey of provider practices and attitudes.

Despite increasing legalization and use of marijuana, there is no consensus among pediatric heart transplant institutions or providers regarding users' eligibility for cardiac transplant. We sent a survey to pediatric and ACHD transplant providers (physicians, surgeons, transplant coordinators, and pharmacists) assessing their current institution's policies and their personal opinions about marijuana use in patients being considered for heart transplantation. Of the respondents, 84% practice in the United States and Canada. Most providers (80%) care for both pediatric and ACHD patients. Respondents included cardiologists (77%) and surgeons (11%), with the remaining being coordinators and pharmacists. Most providers (73%) reported their institution had no policy regarding marijuana use in heart transplant candidates. Only 20% of respondents' institutions consider mode of consumption, with 87% and 53% approving of oral and transdermal routes, respectively, and only 7% approving of vaporized or smoked routes. While 73% of providers would consider illegal marijuana use an absolute/relative contraindication to heart transplant listing, the number decreases to 57% for legal recreational users and 21% for legal medical users. Most providers personally believe marijuana to be physically and mentally/emotionally harmful to pediatric patients (67% and 72%, respectively). Many institutions lack a policy regarding marijuana use in pediatric and ACHD heart transplant candidates, and there is considerable disagreement among providers on the best practice. With increasing legalization and use of marijuana, each institution will have to address this issue thoughtfully to continue to provide high-quality, consistent, and equitable care for pediatric and ACHD heart transplant candidates.

Impact and predictors of positive response to desensitization in pediatric heart transplant candidates.

Desensitization, the process of reducing anti-human leukocyte antigen (HLA) antibodies in sensitized patients awaiting heart transplantation (HT), has unclear efficacy in pediatric HT candidates. Pediatric HT candidates listed at our institution between January 1, 2013 and June 30, 2018 were retrospectively evaluated. Sensitization was defined as the calculated panel reactive antibody (cPRA) ≥ 10% with ≥ 1 a strong positive antibody. The desensitization response was defined as a ≥ 25% reduction in the mean fluorescence intensity (MFI) for ≥ 90% of the strong positive antibodies on follow-up panel reactive antibody (PRA) testing before waitlist removal, HT, or death (data available for 13 patients). The HT candidates were categorized as sensitized receiving desensitization therapy (ST, n = 14), sensitized not receiving therapy (SNT, n = 18), or non-sensitized (n = 55). A desensitization response was observed in 8 (62%) of the ST upon repeat PRA testing, with the ST responders receiving more doses of intravenous immunoglobulin (IVIG) (8 vs 2, p < 0.05). The anti-HLA class I antibodies were particularly resistant for non-responders (p = 1.9 × 10-4). The combination of homograft and ventricular assist device was more sensitizing than either alone (p = 3.1 × 10-4). However, these sensitization risk factors did not impact the desensitization response. The ST was associated with a higher likelihood of remaining listed and a longer waitlist time without substantially impacting the HT rate, waitlist mortality, or early post-HT outcomes. Most ST patients had a favorable response to desensitization, with a dose-dependent response observed for IVIG. The anti-HLA class likely impacts the ST response, whereas traditional sensitization risk factors had no impact on the response.

Time for evidence-based, standardized donor size matching for pediatric heart transplantation

BackgroundAccurately predicting cardiac size by other body parameters has long been problematic to determine whether a donor heart will serve a given waitlist candidate, yet hundreds of heart donors are turned down annually for size mismatch. ObjectivesWe sought to describe how donor body weight parameters are currently utilized in cardiac transplantation and its influence on waitlist outcomes. MethodsFrom the United Network for Organ Sharing database, pediatric (age <18 years) heart transplant candidates were divided into lower quartile, interquartile, and upper quartile categories based on final maximum acceptable donor–candidate weight ratio (DCW), expressed as percentage. Baseline characteristics and waitlist outcomes, including monthly offers/candidate and survival were compared. ResultsOverall median DCW was 200% (range, 159%-241%). Patients with congenital heart disease had higher DCW than those with cardiomyopathy (223% vs 203%; P < .001). Number of monthly offers/candidate (5.0, 5.6, and 7.2, respectively; P < .001) increased with quartile of DCW. Posttransplant survival was similar amongst the groups (log-rank P > .05). Subgroup analysis of critically ill children showed a waitlist survival advantage in those listed with a DCW ≥200% (P < .001). ConclusionsDespite substantial practice variation in acceptable donor weight in pediatric heart transplantation, patients listed with variable DCW had similar posttransplant survival. However, in critically ill patients, higher DCW was associated with greater waitlist survival. Better understanding of the importance of donor weight could reduce practice variability and improve organ use and waitlist outcomes for pediatric cardiac transplant candidates.

Dose-Dependent Response to Desensitization in Pediatric Heart Transplant Candidates Assessed by Single Antigen Bead Technology

Purpose The efficacy of desensitization, the process of reducing anti-HLA antibodies in sensitized patients awaiting heart transplantation (HT), is unclear in pediatric HT candidates. Methods To evaluate the impact of DS in pediatric HT candidates, we performed a retrospective analysis of all patients listed for HT between 1/1/10 - 6/30/18 at our institution. Sensitized patients were defined as having a panel reactive antibody (PRA) ≥ 10% and ≥1 strong positive antibody with mean fluorescence intensity (MFI) ≥ 5500. Patients were identified as nonsensitized (NS, n = 55), sensitized but no therapy (S-NT, n = 18), and sensitized undergoing desensitization therapy (S-DS, n = 14). Response to desensitization was defined as ≥25% reduction in the MFI for ≥90% of strong positive antibodies for whom follow up PRA testing was performed prior to delisting, HT, or death (n = 13). Results DS consisted of IVIG and rituximab for all patients; 2 also received bortezomib. DS responders, defined by reduction in antibody burden (n = 8), received on average more doses of IVIG than nonresponders (9 vs 3, p = 0.04). All five S-DS patients that received HT during the study period had a negative flow crossmatch (FXM) and most (80%) would have had a positive FXM with historical serum. All S-DS had history of single ventricle congenital heart disease and homograft exposure. Prior VAD was associated with sensitization severity (mean positive antibodies 75 vs 26, p = 0.01) but not response to DS, and history of ECMO was associated with neither. S-DS compared S-NT were on average more sensitized (mean number of high MFI antibodies 45 vs 21, p = 0.04), waited longer for HT (569 vs 148 days, p = 0.005), and trended towards higher waitlist mortality (36% vs 11%, p = 0.09). NS patients were less likely to have homograft exposure (p Conclusion A favorable response to DS was observed in most patients in this cohort. Homograft and VAD, but not ECMO, were associated with severity of sensitization. IVIG appears to have some benefit, with a dose-dependent effect. Post-HT outcomes for S-DS, S-NT, and NS patients were similar in this study.

Development and Validation of a Pediatric Heart Failure Risk-Prediction Model for Children Listed for Heart Transplantion in the Current Era

Purpose Previous studies have developed validated risk-prediction models for pediatric heart failure (HF). However, ventricular assist device (VAD) use and organ allocation practices have shifted markedly over the last decade for pediatric heart transplant (HT) candidates. We sought to develop and validate a risk-prediction model in a contemporary cohort of pediatric HF patients. Methods Children Results The selected predictive model had 5 categorical variables: mechanical support [ECMO (Odds ratio, OR 6.3), VAD support (OR 1.3), vs no support], ventilator support (OR 2.5), cardiac diagnosis [congenital heart disease (CHD) (OR 2.3), vs. cardiomyopathy], renal dysfunction [dysfunction (OR 2.3), vs. normal], and weight categories at listing [25-50 kg (OR 2.0), 10-25 kg (OR 3.2), 5-10 kg (OR 3.7), and 0-5 kg (OR 5.6), vs. ≥50 kg]. The final model developed using the derivation cohort after internal cross-validation (N=2029; C-statistic 0.83, Hosmer-Lemeshow Goodness of Fit P=0.81) performed well in the independent validation cohort (N=1194, C-statistic 0.81, HL P=0.68), suggesting excellent prediction in a contemporary cohort of pediatric HF patients as shown in the calibration plot in Figure 1. Conclusion This heart failure risk-prediction model using 5 baseline clinical factors at the time of listing has excellent prediction characteristics for 30-day mortality in a contemporary cohort of children. The model may be useful to support decision-making surrounding referral for advanced cardiac therapies including HT and VAD support.

HLA Antibody Titer and C1Q Reactivity Reflect Response to Desensitization and Facilitate Donor Selection

Purpose Recent reports indicate that >50% of pediatric heart transplant (HT) candidates are HLA-sensitized at time of HT. Clinicians have a difficult choice: wait for an ideal organ offer without HLA antibody (Ab) or take the first acceptable offer. Desensitization can be useful to facilitate HT by decreasing or abrogating HLA Ab. We have evolved to use desensitization to evaluate which HLA Ab may be safely crossed and which to avoid. To illustrate our approach, we present: a non-responder, a partial-responder, and a total-responder. Methods HLA Ab analysis was done by Luminex® single antigen bead assay (SAB), with serial dilutions and C1q-fixing assay. Ab ≥2000 MFI by IgG-SAB and ≥500 MFI by C1q-SAB were used to determine the calculated PRA (cPRA). One desensitization cycle consisted of rituximab (x1), bortezomib (BTZ) (x4), and plasmapheresis (x5). Cycles are repeated leaving 2 weeks between last and first doses of each cycle. Results Non-responder (Fig 1A): Bw4/Aw4 sensitized patient did not respond to desensitization. Ab reassessment showed rebound, and after the 3rdcycle the titer increased and Ab was C1q+. The patient received HT with a Bw6/Bw6 donor without Aw4 antigens; no donor specific Ab (DSA) is detected 1 year post-HT. Partial-responder (Fig 1B): selective response for 1 HLA Ab group. Both anti-DR53 and DQ7/DQ8/DQ9 Abs were C1q+. However, DQ7/DQ8/DQ9 Ab had lower baseline titer. After 2 cycles, DR53 Ab did not change while DQ7/DQ8/DQ9 Ab was reduced in titer and became C1q-. HT proceeded with a DQ7+ donor and DSA remains negative 2.5 years post-HT. Total responder (Fig 1C): Ab to all but self HLA. A complete response was seen; by the end of 3rdcycle, most Ab was reduced to low titer and C1q-. HT was done crossing 2 C1q- Abs. No DSA detected 118 days post-HT. Conclusion Multi-dimensional testing of HLA Ab titer and C1q binding and serial monitoring pre- and post-desensitization helps to determine if more treatment is needed and allows for safe HT risk assessment when crossing HLA Abs.

Invited Commentary

Models of posttransplant mortality are common. They are used frequently: for prognostic information for providers and families, benchmarking of individual center results, and public reporting of those results. Each model or score has strengths and weaknesses that are predominantly determined by the data source and the methodology. The score presented in this issue of The Annals of Thoracic Surgery by O’Connor and colleagues [1O'Connor M.J. Glatz A.C. Rossano J.W. et al.Cumulative effect of preoperative risk factors on mortality after pediatric heart transplantation.Ann Thorac Surg. 2018; 106: 561-567Abstract Full Text Full Text PDF Scopus (6) Google Scholar] is paradigmatic of both the potential and the limitations of a single-center retrospective study. By identifying a series of risk factors unavailable to larger datasets, it demonstrates how the use of large dataset models of posttransplant mortality has the potential to dissuade centers from transplanting high-risk pediatric patients. Most prior models and scores predicting posttransplant mortality in children have been developed using large datasets, commonly either the Pediatric Heart Transplant Study or the Organ Procurement and Transplantation Network/United Network for Organ Sharing data [2Almond C.S. Gauvreau K. Canter C.E. Rajagopal S.K. Piercey G.E. Singh T.P. A risk-prediction model for in-hospital mortality after heart transplantation in US children.Am J Transplant. 2012; 12: 1240-1248Crossref PubMed Scopus (66) Google Scholar, 3Schumacher K.R. Almond C. Singh T.P. et al.Predicting graft loss by 1 year in pediatric heart transplantation candidates: an analysis of the Pediatric Heart Transplant Study database.Circulation. 2015; 131: 890-898Crossref PubMed Scopus (49) Google Scholar, 4Davies R.R. Russo M.J. Mital S. et al.Predicting survival among high-risk pediatric cardiac transplant recipients: an analysis of the United Network for Organ Sharing database.J Thorac Cardiovasc Surg. 2008; 135 (155.e1–2): 147-155Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar]. Organ Procurement and Transplantation Network/United Network for Organ Sharing data underlie the risk prediction models utilized by the Scientific Registry of Transplant Recipients to develop the publicly available program-specific reports (PSRs) evaluating individual center performance. These large-dataset models have the advantage of large sample sizes from multiple centers, but often lack relevant clinical information. Using a single-center retrospective analysis, O’Connor and colleagues [1O'Connor M.J. Glatz A.C. Rossano J.W. et al.Cumulative effect of preoperative risk factors on mortality after pediatric heart transplantation.Ann Thorac Surg. 2018; 106: 561-567Abstract Full Text Full Text PDF Scopus (6) Google Scholar] have identified several risk factors for posttransplant mortality that are not available in larger datasets, including single ventricle congenital heart disease, pulmonary vein stenosis, a history of greater than or equal to 4 prior sternotomies, and referral from another cardiac surgical center. Unfortunately, the methodology limits the practical applicability of the resultant score: the score is unvalidated, it suffers from the biases of the center (eg, there was only a single patient with renal insufficiency), and the increase in mortality occurred predominantly among patients with 4 or 5 risk factors (78% versus 7% to 14% in those with 0 to 3 risk factors). As the authors note, further study and validation of the score is required. However, the inclusion of these granular and specific clinical risk factors does point to the limitations of the current system of public reporting and program monitoring. Accurate models require accounting for all relevant risk models. The Scientific Registry of Transplant Recipients models used in generating PSRs fail to account for many factors that this study and others suggest are associated with high post-transplant mortality: pulmonary vein stenosis, specific congenital diagnoses, a high number of prior sternotomies, and other anatomic abnormalities. When PSRs and similar modeling are used for public reporting, regulatory oversight, and insurance contracting, centers become incentivized to avoid transplanting candidates whose risk factors are not accounted for in the modeling. Thus, while the specific score developed by O’Connor and colleagues [1O'Connor M.J. Glatz A.C. Rossano J.W. et al.Cumulative effect of preoperative risk factors on mortality after pediatric heart transplantation.Ann Thorac Surg. 2018; 106: 561-567Abstract Full Text Full Text PDF Scopus (6) Google Scholar] may have limited wider applicability, the identification of these granular risk factors and their inclusion in modeling is critical both to maximizing individual outcomes and to maintaining access to transplantation among high-risk patients. Cumulative Effect of Preoperative Risk Factors on Mortality After Pediatric Heart TransplantationThe Annals of Thoracic SurgeryVol. 106Issue 2PreviewRisk assessment in heart transplantation is critical for candidate selection, but current models inadequately assess individual risk of postoperative mortality. We sought to identify risk factors and develop a scoring system to predict mortality after heart transplantation in children. Full-Text PDF

Pediatric heart transplantation across a positive crossmatch: First year results from the CTOTC-04 multi-institutional study.

Sensitization is common in pediatric heart transplant candidates and waitlist mortality is high. Transplantation across a positive crossmatch may reduce wait time, but is considered high risk. We prospectively recruited consecutive candidates at eight North American centers. At transplantation, subjects were categorized as nonsensitized or sensitized (presence of ≥1 HLA antibody with MFI ≥1000 using single antigen beads). Sensitized subjects were further classified as complement-dependent cytotoxicity crossmatch (CDC-crossmatch) positive or negative and as donor-specific antibodies (DSA) positive or negative. Immunosuppression was standardized. CDC-crossmatch-positive subjects also received perioperative antibody removal, maintenance corticosteroids, and intravenous immunoglobulin. The primary endpoint was the 1year incidence rate of a composite of death, retransplantation, or rejection with hemodynamic compromise. 317 subjects were screened, 290 enrolled and 240 transplanted (51 with pretransplant DSA, 11 with positive CDC-crossmatch). The incidence rates of the primary endpoint did not differ statistically between groups; nonsensitized 6.7% (CI: 2.7%, 13.3%), sensitized crossmatch positive 18.2% (CI: 2.3%, 51.8%), sensitized crossmatch negative 10.7% (CI: 5.7%, 18.0%), P=.2354. The primary endpoint also did not differ by DSA status. Freedom from antibody-mediated and cellular rejection was lower in the crossmatch positive group and/or in the presence of DSA. Follow-up will determine if acceptable outcomes can be achieved long-term.

Regional variation in the use of 1A status exceptions for pediatric heart transplant candidates: is this equitable?

The use of status exceptions (SE) was recently publicized as a strategy to reduce waitlist times for children awaiting heart transplant (HTx). The aim of this study was to assess SE use across UNOS regions and compare survival in patients listed using a SE to those listed by standard criteria. The OPTN database was queried for all pediatric patients listed for HTx (2000-2014). SE use was compared across UNOS regions. Survival curves were generated and compared using the log-rank test. 1A SE use is uncommon, being utilized in 108 of 4587 pediatric 1A listings (2.4%). There is significant variability in SE use across UNOS regions (0.7%-16.4% of 1A listings, P<.001). Waitlist survival is significantly higher in candidates listed using a 1A SE compared to those listed by standard criteria (P=.001) and is similar to 1B listings. Regional variation in 1A SE use has the potential to introduce bias into a system designed to be equitable. Waitlist survival in patients listed using a SE is similar to those listed status 1B, suggesting these patients may not require 1A status. Careful review of pediatric heart allocation policies is needed to optimize patient outcomes and ensure a fair and unbiased allocation system.

(256) - Regional Variation in the Use of 1A Status Exceptions for Pediatric Heart Transplant Candidates: Is This Equitable?

(256) - Regional Variation in the Use of 1A Status Exceptions for Pediatric Heart Transplant Candidates: Is This Equitable?

Cost-Effectiveness of Pediatric Heart Transplantation Across a Positive Crossmatch for High Waitlist Urgency Candidates

Allosensitized children listed with a requirement for a negative prospective crossmatch have high mortality. Previously, we found that listing with the intent to accept the first suitable organ offer, regardless of the possibility of a positive crossmatch (TAKE strategy), results in a survival advantage from the time of listing compared to awaiting transplantation across a negative crossmatch (WAIT). The cost-effectiveness of these strategies is unknown. We used Markov modeling to compare cost-effectiveness between these waitlist strategies for allosensitized children listed urgently for heart transplantation. We used registry data to estimate costs and waitlist/posttransplant outcomes. We assumed patients remained in hospital after listing, no positive crossmatches for WAIT, and a base-case probability of a positive crossmatch of 47% for TAKE. Accepting the first suitable organ offer cost less ($405 904 vs. $534 035) and gained more quality-adjusted life years (3.71 vs. 2.79). In sensitivity analyses, including substitution of waitlist data from children with unacceptable antigens specified during listing, TAKE remained cost-saving or cost-effective. Our findings suggest acceptance of the first suitable organ offer for urgently listed allosensitized pediatric heart transplant candidates is cost-effective and transplantation should not be denied because of allosensitization status alone.

Predicting graft loss by 1 year in pediatric heart transplantation candidates: an analysis of the Pediatric Heart Transplant Study database.

Pediatric data on the impact of pre-heart transplantation (HTx) risk factors on early post-HTx outcomes remain inconclusive. Thus, among patients with previous congenital heart disease or cardiomyopathy, disease-specific risk models for graft loss were developed with the use pre-HTx recipient and donor characteristics. Patients enrolled in the Pediatric Heart Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis into cardiomyopathy and congenital heart disease cohorts. Logistic regression identified independent, pre-HTx risk factors. Risk models were constructed for 1-year post-HTx graft loss. Donor factors were added for model refinement. The models were validated with the use of patients transplanted from 2007 to 2009. Risk factors for graft loss were identified in patients with cardiomyopathy (n=896) and congenital heart disease (n=965). For cardiomyopathy, independent risk factors were earlier year of transplantation, nonwhite race, female sex, diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and panel reactive antibody >10%. The recipient characteristic risk model had good accuracy in the validation cohort, with predicted versus actual survival of 97.5% versus 95.3% (C statistic, 0.73). For patients with congenital heart disease, independent risk factors were nonwhite race, history of Fontan, ventilator dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower body surface area. The risk model was less accurate, with 86.6% predicted versus 92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor characteristics did not enhance model precision. Risk factors for 1-year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis. Modeling effectively stratifies the risk of graft loss in patients with cardiomyopathy and may be an adjunctive tool in allocation policies and center performance metrics.

(394) - Refusing Donors for HLA Sensitization Reasons Results in Increased Mortality in Pediatric Heart Transplant Candidates

(394) - Refusing Donors for HLA Sensitization Reasons Results in Increased Mortality in Pediatric Heart Transplant Candidates